Activation of Human Alveolar Macrophages via P2 Receptors: Coupling to Intracellular Ca2+ Increases and Cytokine Secretion

Alveolar macrophages play a crucial role in the pathogenesis of inflammatory airway diseases. By the generation and release of different inflammatory mediators they contribute to both recruitment of different leukocytes into the lung and to airway remodeling. A potent stimulus for the release of inf...

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Published in:The Journal of immunology (1950) 2008-08, Vol.181 (3), p.2181-2188
Main Authors: Myrtek, Daniel, Muller, Tobias, Geyer, Verena, Derr, Natalie, Ferrari, Davide, Zissel, Gernot, Durk, Thorsten, Sorichter, Stephan, Luttmann, Werner, Kuepper, Michael, Norgauer, Johannes, Di Virgilio, Francesco, Virchow, J. Christian, Jr, Idzko, Marco
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - pharmacology
Calcium - metabolism
Cytokines - genetics
Cytokines - metabolism
Gene Expression Regulation
Humans
Lipopolysaccharides - pharmacology
Macrophages, Alveolar - drug effects
Macrophages, Alveolar - immunology
Macrophages, Alveolar - metabolism
Receptors, Purinergic P2 - classification
Receptors, Purinergic P2 - genetics
Receptors, Purinergic P2 - metabolism
RNA, Messenger - genetics
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Summary:Alveolar macrophages play a crucial role in the pathogenesis of inflammatory airway diseases. By the generation and release of different inflammatory mediators they contribute to both recruitment of different leukocytes into the lung and to airway remodeling. A potent stimulus for the release of inflammatory cytokines is ATP, which mediates its cellular effects through the interaction with different membrane receptors, belonging to the P2X and P2Y families. The aim of this study was to characterize the biological properties of purinoceptors in human alveolar macrophages obtained from bronchoalveolar lavages in the context of inflammatory airway diseases. The present study is the first showing that human alveolar macrophages express mRNA for different P2 subtypes, namely P2X(1), P2X(4), P2X(5), P2X(7), P2Y(1), P2Y(2), P2Y(4), P2Y(6), P2Y(11), P2Y(13), and P2Y(14). We also showed that extracellular ATP induced Ca(2+) transients and increased IL-1beta secretion via P2X receptors. Furthermore, extracellular nucleotides inhibited production of IL-12p40 and TNF-alpha, whereas IL-6 secretion was up-regulated. In summary, our data further support the hypothesis that purinoceptors are involved in the pathogenesis of inflammatory lung diseases.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.181.3.2181